Sousa-Pinto Bernardo, Bognanni Antonio, Gil-Mata Sara, Vieira Rafael José, Xie Feng, Bonovas Stefanos, Piovani Daniele, Morgano Gian Paolo, Ferreira-da-Silva Renato, Ferreira André, Cardoso-Fernandes António, Lourenço-Silva Nuno, Piggott Thomas, Wiercioch Wojtek, Neumann Ignacio, Bedbrook Anna, Yepes-Nuñez Juan Jose, Klimek Ludger, Zuberbier Torsten, Fonseca João A, Bousquet Jean, Schünemann Holger J
Faculty of Medicine, MEDCIDS - Department of Community Medicine, Information and Health Decision Sciences, University of Porto, Porto, Portugal; CINTESIS@RISE - Health Research Network, Faculty of Medicine, MEDCIDS, University of Porto, Porto, Portugal.
Clinical Epidemiology and Research Center (CERC), Humanitas University & IRCCS Humanitas Research Hospital, Milan, Italy; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
J Clin Epidemiol. 2025 Mar;179:111638. doi: 10.1016/j.jclinepi.2024.111638. Epub 2024 Dec 9.
The evaluation of health benefits and harms of an intervention with GRADE Evidence to Decision (EtD) frameworks includes judgments if the effects are "trivial," "small," "moderate," or "large." Such judgments ideally require the a priori establishment of decision thresholds (DTs), whose empirical derivation for single outcomes has been previously described. In this article, we provide a methodological approach to estimate DTs for composite endpoints based on disutilities.
We generated an approach that involves the computation of pooled disutilities, in which the disutility of each outcome comprised in the composite endpoint is weighted by the respective relative frequency. We also applied a modeling approach based on probability distributions to account for uncertainty in the estimates. We present a practical example of the determination of DTs associated with the development of at least one adverse event following treatment with intranasal medications for rhinitis that we used in the Allergic Rhinitis and its Impact on Asthma guidelines.
We provide the methodological steps of a modeling-based approach to compute pooled disutilities and, as a result, DTs for composite endpoints. We have developed a webtool (https://compositedt.med.up.pt/) that allows for a simple implementation of the proposed approach. Applying our approach to a practical example, we concluded that rhinitis nasal medications, compared to placebo, were associated with a trivial harm from adverse events.
We propose an approach for estimating DTs for composite endpoints, which may be particularly valuable whenever composite endpoints are used for clinical research, clinical practice, and decision-making.
使用GRADE证据到决策（EtD）框架评估一项干预措施的健康益处和危害，包括判断其效果是“微不足道”“小”“中等”还是“大”。理想情况下，此类判断需要事先确定决策阈值（DTs），此前已有针对单一结局的经验性推导方法。在本文中，我们提供一种基于负效用估计复合终点决策阈值的方法。
我们生成了一种涉及计算合并负效用的方法，其中复合终点中每个结局的负效用由各自的相对频率加权。我们还应用了基于概率分布的建模方法来考虑估计中的不确定性。我们给出了一个实际例子，即确定与鼻炎鼻内用药治疗后至少发生一次不良事件相关的决策阈值，我们在《变应性鼻炎及其对哮喘的影响》指南中使用了该例子。
我们提供了一种基于建模的方法的步骤，用于计算合并负效用，从而得出复合终点的决策阈值。我们开发了一个网络工具（https://compositedt.med.up.pt/），可实现所提方法的简单应用。将我们的方法应用于一个实际例子，我们得出结论，与安慰剂相比，鼻炎鼻内用药导致不良事件的危害微不足道。
我们提出了一种估计复合终点决策阈值的方法，在复合终点用于临床研究、临床实践和决策时可能特别有价值。
